Physiology and Pharmacology Flashcards
1
Q
what is the purpose of sphincters?
A
keep food moving aborally, prevent it from going the wrong way
2
Q
what are the accessory structures of the digestive system?
A
salivary glands
pancreas
the liver and the gall bladder (hepatobiliarry system)
3
Q
what are the 4 main digestive processes?
A
motility
secretion
digestion
absorption
4
Q
what are the 3 types of mechanical activity within the GI system?
A
propulsive movements
mixing movements
tonic contractions
5
Q
what are the 2 groups within secretions in the GI tract?
A
digestive secretions
protective secretions
6
Q
what is the process of digestion?
A
biochemical breakdown of complex foodstuffs into smaller, absorbable units
7
Q
what type of enzymes break down carbohydrates?
A
amylases and diasaccharidases
8
Q
what type of enzymes break down proteins?
A
proteases and dipeptidases
9
Q
what type of enzymes break down fats?
A
lipases
10
Q
what is absorption within the GI tract?
A
transfer of absorbable products of digestion (+ water, electrolytes and vitamins) from the digestive tract to the blood or lymph
11
Q
what are the 4 main layers of the digestive tract wall?
A
mucosa
submucosa
muscularis externa
serosa
12
Q
what does the mucosa of the GI tract consist of?
A
epithelial cells exocrine cells endocrine gland cells lamina propria muscularis mucosa
13
Q
what does lamina propria of the mucosa of the GI tract consist of?
A
capillaries,
enteric neurones,
immune cells
14
Q
what does the submucosa of the GI tract consist of?
A
connective tissue
larger blood and lymph vessels
sub mucous plexus (nerve network)
15
Q
what does the muscularis externa of the GI tract comprise of?
A
circular muscle layer myenteric plexus (nerve network) longitudinal muscle layer
16
Q
what does the serosa of the GI tract comprise of?
A
connective tissue
17
Q
which of the GI sphincters are made of skeletal muscle?
A
upper oesophagus sphincter
external anal sphincter
18
Q
what does contraction of the circular muscle of the muscularis externa do to the GI tract?
A
lumen becomes narrower and longer
19
Q
what does contraction of the longitudinal muscle in the muscularis externa do in the GI tract?
A
tract becomes shorter and fatter
20
Q
what does contraction of the muscularis mucosa do to the GI tract?
A
causes changes in the absorptive and secretory area of mucosa
21
Q
how are adjacent smooth muscle cells coupled in order to allow the spread of electrical currents?
A
by gap junctions
22
Q
what 3 things modulate the spontaneous activity of the smooth muscle of the GI tract?
A
intrinsic nerves- enteric
extrinsic nerves- autonomic
hormones
23
Q
what type of spontaneous electrical activity occurs in the stomach, small intestine and large intestine?
A
slow waves
24
Q
what are the pacemaker cells within the stomach, small intestine and large intestine which drive the slow wave electrical activity?
A
interstitial cells of Cajal
25
what has to happen for a slow wave in the stomach, small intestine and large intestine to cause an action potential?
slow wave has to meet the threshold
26
what is force of contraction of the smooth muscle within the GI tract related to?
the number of action potentials discharged
| ie the length of time that the slow wave was above threshold
27
where are interstitial cells of Cajal located?
- between longitudinal and circular muscle layers
| - submucosa
28
when does slow wave activity in the GI tract generally remain in the background and not reach thresholds?
between meals
29
what is the basic electrical rhythm (BER) of the GI tract determined by?
slow wave
30
what are the factors which determine whether a slow wave amplitude reaches threshold/for how long it remains above threshold?
neuronal stimuli
hormonal stimuli
mechanical stimuli
31
using basic electrical rhythm (BER), explain why chyme moves from oral to aboral direction within the small intestine?
higher BER in the duodenum than the terminal ileum
| more vigorous mechanical activity proximally pushes food distally in the small intestine
32
using the basic electrical rhythm (BER), explain why the colon is able to hold contents for a long period of time?
higher BER in the distal colon than the proximal colon
| (more vigorous actiivty distally favours retention of luminal contents(
33
why is it important that the colon holds food for a long period of time?
to allow for absorption of enough water and electrolytes
34
what neurones is the enteric nervous system made of?
sensory neurones
interneurones
effector neurones
35
where are the ganglia that the parasympathetic supply to the GI tract synapse at?
within the ENS
36
what excitatory influences does parasympathetic supply to GI tract have?
increases secretions
increases blood flow
generally increases smooth muscle contraction
37
what inhibitory influences does parasympathetic supply to the GI tract have?
relaxation of some sphincters
| receptive relaxation of stomach
38
where are the ganglia that the sympathetic supply to the GI tract synapse at?
prevertebra ganglia
39
what inhibitory influences does the sympathetic supply to the GI tract have?
decreased motility
decreased secretions
decreased blood flow
40
what triggers the receptive relaxation of the stomach?
food entering the oesophagus
41
where does the sensory neurone synapse with the interneurone in a local reflex of the GI tract?
within the myenteric plexus or submucous plexus
42
where does the sensory neurone synapse with the interneurone in a short reflex of the GI tract?
at a preverterbal ganglion
43
where does the sensory neurone synapse with the interneurons in a long reflex of the GI tract?
at a dorsal motor nucleus of the vagus in the medulla oblongota
44
what type of GI reflex is peristalsis?
```
local reflex
(intrinsic)
```
45
what type of GI reflex is a interstino-intestinal inhibitory reflex?
short reflex
46
what type of GI rexles is a gastroileal reflex?
long reflex
47
what is the gastroileal reflex?
occurs when food enters the stomach causing vigorous mechanical activity in the stomach.
this sends a reflex response to cause contraction of the ileum to remove the previous food remnants from the small intestine
48
what is peristalsis?
an orderly wave of contraction (squeeze from behind bolus, relax in front) to push food in the aboral direction
49
what is peristalsis reflexively triggered by?
distension of the gut wall
50
what 2 neurotransmitters released from an inhibitory motoneurone cause smooth muscle within the muscularis externa to relax?
VIP (vasoactive peptide)
| NO (nitrate)
51
what neurotransmitter released from an excitatory motoneurone causes smooth muscle within the muscularis externa to contract?
ACh
52
in peristalsis, what do the muscle layers within the muscularis externa do to cause contraction behind the bolus?
circular muscle contracts (under ACh control)
| longituidinal muscle relaxes (under VIP and NO control)
53
in peristalsis, what do muscle layers within the muscularis externa do to cause relaxation in front of the bolus?
circular muscle relaxes (under VIP and NO control)
| longituidinal muscle contracts (under ACh control)
54
what is sementation?
rhythmic contractions of the circular muscle layer that mixes and divides luminal contents
55
where does segmentation occur?
in small intestine (fed state)
| in large intestine
56
what is segmentation called within the large intestine?
haustration
57
what type of contractions do sphincter muscles of the GI tract go through?
tonic contractions
58
how does segmentation occur?
circular muscle layer is contracted at 2 points
| between these 2 points the muscle is relaxed
59
why does a sphincter open?
if proximal pressure is greater than distal pressure
60
what are the 6 sphincter of the GI tract? (excluding sphincter of oddi)
```
upper oesophageal sphincter
lower oesophageal sphincter
pyloric sphincter
ileocecal sphicter
internal anal sphincter
external anal sphincter
```
61
why does vomiting cause the reflux of duodenal gastric contents?
vomitting relaxes the pyloric sphincter
62
why does the upper oesophageal sphincter close during inspiration?
to prevent large amounts of air entering the oesophagus
63
what disease occurs in the lower oesophageal sphincter doesn't function properly?
gastro-oesophageal reflux disease
64
what is the function of the palate of the mouth?
separates mouth from nasal passages to allow breathing and chewing simultaneously
65
what is the function of the uvula?
helps seal off nasal passages during swallowing
66
what is the function of the tongue?
guides food, important in speech and swallowing, major location of taste buds
67
what are the tonsils on the side walls of the pharynx?
lymphoid tissues
68
what is mastication?
chewing
69
what is the function of the masseteric reflex?
jaw opening
70
what is the function of the diagastric reflex?
jaw closing
71
what stimulates the pharyngeal receptors to send an afferent impulse to the swallowing centre in the medulla?
pressure from the food bolus
72
what happens to the soft palate, tongue, uvula during swallowing and why?
soft palate raises
tongue presses against the hard palate
uvula presses against back of throat
(to prevent food entering nasal passages)
73
what happens to the larynx, epiglottis, vocal cords during swallowing and why?
larynx elevates
epiglottis tilts
vocal cords close across the larynx opening
(to prevent food entering the trachea)
74
what centre in the brain does the swallowing centre inhibit during swallowing and why?
the respiratory centre
| to prevent food entering the trachea
75
where is the swallowing centre within the brain?
medulla oblongata
76
once the food bolus has entered the oesophagus, what triggers the closure of the upper oesophageal sphincter?
swallowing centre
77
what do local pressure receptors within the oesophagus stimulate when food has become lodged?
stimulate a secondary peristaltic wave (more forceful than primary)
increase saliva production
78
what are the 3 major salivary glands that saliva is secreted from?
parotid gland
submandibular gland
sublinual gland
79
what are the 6 important functions of saliva?
```
lubrication
solvent
antibacterial
digestion of complex carbohydrates
neutralisation of acid
facilitates sucking by infants
```
80
what is the solvent function of saliva important for?
taste
81
what 3 important antibacterial substances does saliva contain?
lysozyme
lactoferrin
immunoglobulins
82
what is the job of lactoferrin?
binds iron needed for bacterial replication
83
what important salivary substance is important in the digestion of complex carbohydrates?
amylase
84
what important salivary substance is important in the neutralisation of acid?
bicarbonate
85
how does saliva facilitate sucking by infants?
fluid seal
86
what are the 2 stages of the formation of saliva?
primary secretion
| secondary modification
87
what cells are important in the primary secretion phase of saliva formation?
acinus
88
what cells are important int he secondary modification phase of saliva formation?
duct cells
89
what occurs in the primary secretion phase of saliva formation?
acinus cells produce a primary secretion with Na+, K+, Cl- and HCO3- content similar to plasma, plus mucus and amylase
90
what occurs in the secondary modification phase of saliva formation?
duct cell modify acinus secretion by removing Na+ and Cl- (and to a lesser extent adding K+ and HCO3-)
there is no movement of H2O, but there is an overal diluting phase
91
why is there no movement of water in the secondary modification phase of saliva formation?
epithelium is impermeable to water
92
why is important that the NaCL content of saliva is much lower than plasma?
to allow detection of salty taste
93
as the flow rate of saliva increases, what happens to the concentration of HCO3- within it?
as saliva flow rate increases HCO3- content of saliva increases
94
what are the 2 types of reflexes which increase the rate of saliva formation?
```
simple reflex (saliva increased in response to food in mouth)
conditioned reflex (saliva increased in response to a certain stimuli which suggests food is coming-acquired)
```
95
in normal saliva production which section of the autonomic nervous system has a dominant role?
parasympathetic stimulation
96
what type of saliva is produced when parasympathetic stimulation has a dominant role?
a large volume of enzyme rich, watery saliva
97
what receptors mediate the parasympathetic control on saliva production?
M3 muscarinic acetylcholine receptors
98
during stressful times which section of the autonomic nervous system has dominant control?
sympathetic system
99
what type of saliva is produced when sympathetic stimulation has a dominant role?
a small volume of mucus rich, thick saliva
100
what receptors mediate the sympathetic control on saliva production?
B1-adrenoceptors
101
what are the 4 main areas of the stomach?
fundus
body
antrum
pylorus
102
what happen to the rugae when the stomah fills up?
they smooth out
103
what is retropulsion with respects to the mixing of contents in the stomach?
food in the body of the stomach is propelled forward by peristaltic waves. chyme hits the pyloric area and bounces back
104
what hormone stimulated the release of HCl?
gastrin
105
how can duodenum delay emptying?
neuronal response
| hormonal responce
106
what is the function of the enterogastric reflex?
decreases antral peristaltic activity to delay emptying of the stomach
107
what does the release of enterogastrones (secretin, CCK) from the duodenum do to the emptying of the stomach?
release of enterogastrones inhibit stomach contraction and so delay emptying of the stomach
108
what 4 things within the duodenum drive neuronal and hormonal responses to delay gastric emptying?
fat
acid
hypertonicity
distension
109
what major secreting cells are within the pyloric gland area (PGA) in the antrum of the stomach?
D cells
G cells
mucosal cells
110
what do D cells within the pyloric gland area in the antrum of the stomach secrete?
somatostatin
111
what do G cells within the pyloric gland area in the antrum of the stomach secrete?
gastrin
112
what secreting cells are within the oxyntic mucosa (OM) in the fundus and body of the stomach?
chief cells
enterochromaffin-like cells
parietal cells
113
what do chief cells within the oxyntic mucosa in the fundus and body of the stomach secrete?
pepsinogen
114
what do enterochromaffin-like cells within the oxyntic mucosa in the fundus and body of the stomach secrete?
histamine
115
what do parietal cells within the oxyntic mucosa in the fundus and the body of the stomach secrete?
hydrocholic acid
| intrinsic factpr
116
what is the function of HCl secreted from parietal cells of the oxyntic mucosa?
1. activates pepsinogen to pepsin
2. denatures protein
3. kills most micro-organisms
117
what is the function of pepsinogen secreted from chief cells of the oxyntic mucosa?
inactive precursor of pepsin
| once pepsin is formed it is autocatalytic and so activated pepsinogen
118
what is the function of intrinsic factor secreted from parietal cells of the oxyntic mucosa?
binds to vitamin B12 allowing absorption in terminal ileum
119
what is the function of histamine secreted from enterochromaffin-like cells of the oxyntic mucosa?
stimulates HCl secretion from parietal cells
120
what is the function of gastrin secreted from the G cells of the pyloric gland area?
stimulates HCl secretion from parietal cells
| stimulates histamine production from enterochromaffin-like cells
121
what is the function of somatostatin secreted from D cells of the pyloric gland area?
inhibits secretion of gastrin from G cells to decrease HCl production from parietal cells
122
why is somatostain important?
reduced concentrations of acid going into the duodenum
123
what is the function of mucus secreted from mucosal cells of the pyloric gland area?
protect the mucosa
| otherwise ulcers can form
124
what type of secretions are somatostatin and gastrin?
endocrine (into blood stream)
125
what is the function of prostaglandin (PGE2) on parietal cells?
inhibits parietal cell secretions
126
what is the effect of cholinergic stimulation of M1 receptors on enterochromaffin-like cells?
increase histamine secretion
127
what is the effect of cholinergic simulation of M3 receptors on parietal cells?
increase HCl secretion
128
where are the ion ATPase pumps in a resting parietal cell?
within cytoplasmic tubulovesicles
129
where are the ion ATPase pumps in a stimulated parietal cell?
they trafficked to the apical membrane and sit in the extended microvilli
130
what are the 3 phases of gastric secretion?
cephalic
gastric
intestinal
131
when is the cephalic phase of gastric secretion?
before food reaches the stomach
132
when is the gastric phase of gastric secretion?
when food is in the stomach
133
when is the intestinal phase of gastric secretion?
after food has left the stomach
134
what is the effect of cholinergic simulation of M receptors on D cells?
decreased somatostatin production
135
what is the main effect off the intestinal phase on acid secretion?
switches it off
136
what 3 classes of drugs decrease hydrochloric acid secretion?
muscarinic receptor competitive antagonists (no longer used)
H2 histamine receptor competitive antagonists
Proton-pump inhibitors
137
how do proton-pump inhibitors work?
covelent modification of a K+/H+ ATPase on the apical membrane of parietal cells
138
what class of drugs increases hydrochloric acid secretion?
NSAIDs (eg aspirin, ibuprofen etc)
139
how do NSAIDs work to increase HCl secretion?
by blocking COX irreversibly which results in decreased prostaglandins
140
what is the function of PGE2 and PGI2 in the stomach? (locally produced prostaglandins)
reduced acid secretion
increase mucus secretion
increase bicarbonate secretions
increase mucosal blood flow
141
what 2 things can NSAIDs trigger due to the fact they reduce prostaglandins?
ulceration
| bleeding
142
how can gastric damage due to long-term NSAID treatment be prevented?
using a stable PGE1 analogue (eg misoprostol)
143
what do PGE1 analogues do?
inhibit basal and food-stimulated gastric acid formation
| maintains/increases secretion of mucus and bicarbonate
144
what bacterium can cause chronic infection of the gastric antrum and is associated with peptic ulcers?
Helicobacter pylori
145
why does H. pylori predispose to peptic ulcers?
causes persistent inflammation that weakens the mucosal barrier leaving the submucosa subject to attack by HCl and pepsin
146
why are PPIs called prodrugs?
because they are inactive at neutral pH but change conformation in a strongly acidic environment
147
how do PPI's get to the secretory cannaliculi?
absorbed from the GI tract and delivered via the systemic circulation
148
what are ranitidine and cimetidine?
H2 receptor antagonists
149
how are H2 receptor antagonists administered?
PO
150
what is sucralfate?
a mucosal strengthener
151
what is bismuth chealate?
a mucosal strengthener which is also toxic towards H. pylori
152
what drug is bismuth chealate usually administered with?
ranitidine
153
what type of carbohydrates are indigestible in humans?
cellulose
154
what are the 2 sub-groups of starch?
amylose
| amylopectin
155
what type of carbohydrates are sucrose and lactose?
disaccharides
156
what endogenous sources of proteins are also ingested?
digestive enzymes (ie once role has been fufilled) and dead cells from GI tract
157
what are the 3 main digestive processes that occur in the small intestine?
luminal digestion
membrane/brush border digestion
intracellular digestion (in enterocyte)
158
what is luminal digestion in the small intestine mediated by?
pancreatic enzymes secreted into the duodenum
159
what is membrane/brush border digestion in the small intestine mediated by?
enzymes situated at the brush border of enterocytes
160
what are enterocytes?
absorptive cells of the intestinal epithelium
161
assimilation =
digestion + absorption
162
what is the movement of substances across the epithelial tight junctions called?
paracellular movement
163
what is the movement of sybstances through enterocytes called?
intracellular movement
164
what substances can actually move through the tight junctions between the enterocytes?
ions
165
what type of carbohydrates are glucose and fructose?
monosaccharides
166
compare amylose and amylopectin in terms of linkages?
amylose- linear straight chain: a1-4 linkages
| amylopectin- branched chain: a1-4 and a1-6 linkages
167
which is more highly branched? (glycogen or amylopectin)
glycogen
| glycogen has more a1-6 linkages than amylopectin
168
in sucrose, what are glucose and fructose linked by?
a1-2 linkages
169
in lactose, what are glucose and galactose linked by?
b1-4 linkages
170
in an alpha glucose molecule, on C1, where is the hydroxyl group?
below
171
in a beta glucose molecule, on C1, where is the hydroxyl group?
above
172
what must dietary carbohydrates be converted to for absorption into the enterocyte?
monosaccharides
173
what type of digestion do polysaccharides (eg starch) go through to form oligosaccharides?
intraluminal hydrolysis
174
what type of digestion do oligosaccharides (eg sucrose and lactose) go through to form monosaccharides?
brush border hydrolysis
175
what enzymes are involved in the intraluminal hydrolysis of polysaccharides (eg starch)?
salivary a-amylase
| pancreatic a-amylase
176
what 4menzymes are involve in the brush border digestion of oligosaccharides?
oligosaccharidases:
lactase
maltase
sucrase-isomaltase
177
what is maltose made of?
2 glucose monomers
178
what is maltotriose made of?
3 glucose monomers
179
what is special about sucrase-isomaltase?
2 different enzymes with 2 different substrates but in the form of one combines macro-molecule
180
what linkages can a-amylase break down?
| what linkages can it not break down?
a1-4 internal linkages
(not a-1-4 terminal linkages or a1-6 linkages or a1-4 linkages adjacent to branch points:
this is why monosaccharides aren't formed)
181
what is an endoenzyme?
only breaks down internal linkages but not terminal linkages
| eg a-amylase
182
what is the unique function of lactase?
breaks down lactose to glucose and galactose
| b1-4 bond hydrolysis
183
what is the unique function of sucrase?
breaks down sucrose to glucose and fructoase
| a1-2 bond hydrolysis
184
what is the unique function of isomaltase?
breaks down a1-6 linkages
185
what 3 oligosaccharides, in addition to their unique function, can cleave terminal a1-4 terminal linkages?
maltase
| sucrase-iso-maltase
186
what is the rate-limiting step of assimilation for maltase, sucrase and isomaltase?
transport process
187
what is the rate-limiting step of assimilation for lactase?
the hydrolysis of lactose
188
what is lactose intolerance caused by?
lactase insufficiency
189
what is primary lactase deficiency? (primary hypolactasia)
lactose intolerance due to lack of lactase persistence (LP) allele
190
what is secondary lactase deficiency?
lactose intolerance due to damage to proximal small intestine
191
what is congenital lactose deficiency?
rare autosomal recessive disease, no ability to digest lactose from birth
192
why are some humans able to digest lactose after weaning?
| lactase activity is generally lost in mammals after weaning- primary lactase deficiency
these individuals have a variable degree of lactase persistance due to polymorphisms
193
when does hypolactasia cause problems?
lactose-containg food is consumed in amounts that overwhelm the activity of remaining lactase
194
if lactose is delivered to the colon in a person with hypolactasia what happens?
colonic microflora feed on the lactose and produce:
short chain fatty acids (which can be absorbed)
hydrogen
carbon dioxide
methane
195
what is the result of the products produced by colonic microflora feeding on lactose?
bloating
abdominal pain due to distension
flatulence
196
what 2 things does undigested lactose cause?
acidification of the colon
| an increased osmotic load causing diarrhoea
197
where does absorption of monosaccharides take place?
duodenum
| jejunum
198
how are glucose and galactose absorbed across the apical membrane of an enterocyte?
secondary active transport mediated by SGLT1
199
how is fructose absorbed across the apical membrane of an enterocyte?
facilitated diffusion mediated by GLUT 5
200
how do all monosaccharides exit the basal membrane of an enterocyte?
facilitated diffusion mediated by GLUT 2
201
what is secondary active transport?
the movement of a substance coupled to the movement of ions in the ATPase
202
which type of glucose can be absorbed?
ring glucose not linear glucose
203
how far must protein be digested to enable absorption into enterocyte?
to oligopeptides and amino acids
204
what are the 3 pathways for protein digestion?
1. a) protein digested to amino acids by luminal enzymes
2. a) protein digested to peptides by luminal enzymes
b) peptides digested to amino acids by brush border enzymes
3. a) protein digested to peptides by luminal enzymes
b) peptides digested to amino acids by intracellular hydrolysis
205
what are the 5 pancreatic proteases?
```
trypsin
chymotrpin
elastase
procarboxypeptidase A
procarboxypeptidase B
```
206
which pancreatic proteases are endopeptidases (target internal bonds) and which are exopeptidase (target terminal bonds)?
endopeptidase- trypsin, chymotrypsin, elastase
exopeptidase- procarbosypeptidase A, procarboxypeptidase B
207
what are the products of endopeptisases?
oligopeptides (2-6 amino acids chain)
208
what are the products of exopeptidases?
single amino acids
209
are aminopeptidases exopeptidases of endopeptidases?
exopeptidase
210
how many different amino acid absorption mechanisms are present at the brush border of the enterocyte?
7
5 Na dependent (Secondary active transport)
2 Na independent
211
how many different amino acid transport mechanisms are present at the basal membrane of the enterocyte?
5 (bidirectional)
3 Na independent and mediate efflux
2 Na dependent and mediate influx
212
how are oligopeptides transported across the apical membrane of an enterocyte?
via H+ dependent mechanisms (secondary active transport)
213
what is the lingual phase of digestion?
when food is in the mouth
214
why is HCO3 in pancreatic juice important for the digestion of fats?
neutralises stomach acid to provide a suitable pH for pancreatic lipase
215
what hormone is bile secreted in response to?
CCK
216
what is the function of bile salts?
emulsification of large lipid droplets to small lipid droplets
(increased surface area for action of lipase)
217
what does failure to secrete bile salts result in?
1. lipid malabsorption
| 2. secondary vitamin deficiency due to failure to absorb lipid vitamin
218
what stool sign indicated the patient has lipid malabsorption?
steatorrhoea
219
why is co-lipase important?
because without co-lipase bile salts block access of lipase to the lipid- co-lipase binds to both bile salts and lipase to allowing access to the lipids
220
where is co-lipase produced?
pancreas
221
what are the final products of lipid digestion (eg fatty acids, monoglycerides, phospholipids) stored in?
mixed micelles
222
how do micelles enter the enterocyte?
passive diffusion
223
what apolipoprotein joins the forming chylomicron?
apo-B48
224
what transport protein carries cholesterol across the enterocyte apical membrane?
NPC1L1
225
what is the function of ezetimibe?
binds to NPC1L1 to prevent internalisation of cholesterol
226
how does the absorption of Ca++ occur?
passive transport
| active transport
227
what does the passive transport of calcium across the epithelium involve?
paracellular movement
228
where does paracellular movement of Ca++ occur in the GI tract?
whole length of the small intestine
229
what does active transport of calcium across the epithelium involve?
transcellular movement through a calcium channel
230
where does transcellular movement of Ca++ occur in the GI tract?
duodenum and upper jejunum
231
when there is a low lumenal concetration of calcium what way is calcium transported?
transcellular movement (Calcium channels)
232
when there is a high lumenal concentration of calcium what way is calcium transported?
paracellular movement
233
how is iron transported across the epithelium of the intestines?
transcellularly by metal transporter
234
how is haem transported across the epithelium of the intestines?
transcellularly by haem transporter
235
what form does iron need to be in to be transported into the enterocyte by the metal transporter?
Fe2+
236
what reduces the iron from Fe3+ to Fe2+ in the gut?
vitamin C
237
how does Fe2_ leave the enterocyte?
via feroportin
238
what is the function of hepcidin?
it is released from the liver when body iron levels are high and negatively regulates ferroporitin
239
what causes vitamin B12 to be released from food?
stomach acid
240
what binds to the vitamin B12 once released in the stomach?
haptocorrin
241
where is haptocorrin produced?
salivary glands
242
what happens to the haptocorrin-vitB12 complex in the small intestine?
pancreatic proteases digest the haptocorrin and vitamin B12 is released
243
what binds to vitamin B12 in the small intestine?
intrinsic factor
244
what is the function of intrinsic factor?
forms a complex with B12 and allows it to be absorbed in the terminal ileum by endocytosis
245
how are fat soluble vitamins absorbed across the epithelium of the intestine?
incoporated into mixed micelles and passively transported into enterocytes
246
once inside the enterocyte, what is the journey of fat-soluble vitamins?
incorporated into chylomicrons and distributed by lymphatics
247
how are water soluble vitamins absorbed across the epithelium?
active transport
248
what cause motion sickness?
sensory conflict regarding position of body in space
| inner ear senses movement but brain thinks we have not moved
249
why is pregnancy-induced nausea and vomiting (in the first trimester) an adaptive advantage?
encourages picky eating during a time of rapid foetal growth
250
what type of pregnancy-induced vomiting outlasts first trimester and can be extremely damaging to both mum and baby?
hyperemesis gravidarum
251
what is emesis (vomiting)?
the forceful propulsion of gastric contents out of the mouth
252
during emesis, what state are the stomach, oesophagus and associated sphincter in?
relaxed state
253
what part of the medulla oblongata in the brain stem co-ordinates vomiting?
the vomiting centre
254
describe the vomiting cycle?
1. suspension of intestinal slow wave activity
2. retrograde contractions from ileum to stomach
3. deep inhalation
4. suspension of breahing
5. relaxation of LOS + contraction of diaphragm and abdominal muscles
6. ejection of gastric contents through open UOS
7. repeated until relief is felt
255
why during emesis is breathing suspended and the rima glottis closed?
to prevent aspiration
256
during emesis, what is the purpose of the contraction of diaphragm and abdominal muscle?
increases pressure in abdominal cavity and compresses stomach
257
what usually precedes vomiting?
profuse salivation
sweating
elevated heart rate/force
nausea
258
what is retching?
the mechanical process of vomiting but no substance (stomach is already empty)
259
what do toxic materials in the gut/systemic toxins causes the release of?
seretonin from enterochromaffin cells in mucosa
260
what does the seretonin released in response to a toxin cause?
depolarisation of sensory afferent terminals in mucosa via 5-HT3 receptors causing an vagal afferent action potential discharge to brainstem
261
what particular areas in the brainstem are vagal vomiting-inducing afferent discharges sent to?
(these cause co-ordination of vomiting by the vomiting centre)
CTZ-chemoreceptor trigger zone
| NTS- nucleus tractus solitarius
262
how can toxic materials within the blood stimulate the chemoreceptor trigger zone to cause vomiting without APs?
CTZ lacks an effective blood brain barrier so the toxic materials can stimulate it directly
263
what 2 types of stimuli can send vagal afferents to the brain stem to cause the co-ordination of the vomiting centre?
```
chemical stimuli (via 5HT3 receptors)
mechanical stimuli
```
264
how does the vestibular system signal to the vomiting centre to cause the co-ordination of vomiting? (motion sickness)
signalls through vestibular nuclei to chemoreceptor trigger zone
and then to vomiting centre
265
what type of stimuli can cause co-ordination of vomiting by the vomiting centre via the medulla and cerebral cortex limbic system?
stimuli within the CNS itself
| eg pain, repulsive sights/odours, fear etc
266
what are the 5 consequences of severe vomiting?
1. dehydration
2. hypochloraemic metabolic alkalosis
3. hypokalaemia
4. (Rarely) metabolic acidosis
5. (rarely) malloey-weiss tear
267
why does severe vomiting cause hypochloraemic metabolic alkalosis?
loss of gastric protons and chloride (ie HCL)
268
why does severe vomiting cause hypokalaemia?
proton loss causes the kidneys to excrete potassium
269
why can severe vomiting sometime cause metabolic acidosis?
because of los of duodenal bicarbonate
270
why does cancer chemotherapy and radiotherapy cause nausea and vomiting?
induces release of 5-HT and substance P from enterochromaffin cells in the gut
271
why can medications used in parkinsons disease cause nausea and vomiting?
because these drugs have high dopamine activity
| dopamine D2 receptors are prevalent in the chemoreceptor trigger zone
272
why can anti-depressants such as selective serotonin reuptake inhibitors cause nausea and vomiting?
because they enhance 5-HT function
| 5HT3 receptors are prevalent in the chemoreceptor trigger zone
273
what are the 6 major classes of antiemetic drugs?
```
5HT3 receptor antagonists
Muscarinic ACh receptor antagonists
Histamine H1 receptor antagonists
Dopamine receptor antagonists
NK1 receptor antagonists
Cannabinoid receptor agonists
```
274
how do 5HT3 receptor antagonists work in the prvention of emesis?
block peripheral and central 5HT3 receptors
275
what are 5HT3 receptor antagonists used for?
- to supress chemothrapy and radiation induced emesis
| - to reduced post-operative emesis
276
5HT3 receptor antagonists become less effective during subsequent treatments, how is function improved?
by the addition of a corticosteroid and NK1 receptor antagonist
277
How do muscarinic acetylcholine receptor antagonists work in the prevention of emesis?
- block muscarinic acetylcholine receptors at multiple sites (eg vestibular nuclei, NTS, vomiting centre)
- direct inhibition of GI movement
278
what are anti-emetic muscarinic acetylcholine receptor antagonists used for?
prophylaxis and treatment of motion sickness
| transdermal or PO
279
what are the adverse effects of antiemetic muscarinic acetylcholine receptor antagonists?
many unwanted effects from parasympathetic blockade
| centrally-mediated sedation
280
how do H1 receptor antagonists work?
block of histamine receptor 1 in vestibular nuclei and NTS
| H1 receptors are important in allergic effect and emetic effect
281
what are anti-emetic H1 receptor antagonists used for?
prophylaxis and treatment of motion sickness
282
what are the adverse effects of anti-emetic H1 receptor antagonists?
CNS depression and sedation
283
how do dopamine receptor antagonists work?
centrally block dopamine D2 and D3 receptors in the CTZ
284
compare the adverse effects of domperidone and metoclopramide?
domperidone doesn't cross blood brain barrier unlike metoclopramide so has less unwanted effects
285
what are dopamine receptor antagonists used for?
drug-induced vomiting
| and vomiting in GI disorders
286
when should dopamine receptor antagonists be avoided?
in children
287
how do NK1 receptor antagonists work?
antagonism of substance P
288
when are cannabinoid receptor agonists used?
in cytotoxic chemotherapy that is unresponsive to other anti-emetics
289
what are the adverse effects of cannabinoid receptor agonists
drowsiness, dizziness, dry mouth, mood changes
290
what is the name for the intestinal juice that the small intestine secretes?
succus entericus
291
where do the bile duct and pancreatic duct meet?
ampulla of Vater
292
where is gastrin produced in the duodenum?
from G cells
293
where is cholecystokinin produced?
from I cells of duodenum and jejunum
294
where is secretin produced?
from S cells of the duodenum
295
where is motilin produced?
from M cells of the duodenum and jejunum
296
where is glucagon-like insulinotropic peptide (GIP- gastric inhibitory peptide) produced?
from K cells of duodenum and jejunum
297
where is glucacon-like peptide-1 (GLP-1) produced?
from L cells of the gut
298
where is ghrelin produced?
from Gr cells of the gastric antrum and small intestine
299
what are incretins?
hormones which act upon the beta-cells of the pancreas in a feed-forward way to stimulate the release of insulin
300
which hormones produced from the duodneum are incretins?
glucagon-like insulinotropic peptide (GIP- gastric inhibitory peptide)
glucagon-like peptide-1 (GLP-1)
301
when are incretins (GIP and GLP-1) from the duodenum released?
in response to chyme entering the duodenum
302
what does the succus entericus contatin?
mucus
aqueous salts
(no digestive enzymes)
303
where is mucus from the duodenum produced?
goblet cells
304
where are the aqueous salts secreted in the duodenum from?
crypts of lieberkihn
305
how does chloride get into the enterocytes?
sodium potassium chloride co-transporter on basolateral membrane
(Na, 2Cl, K enters cell)
306
what is the function of the sodium potassium chloride co-transporters on the basolateral membrane?
to increase the intracellular concentration of chloride to allow chloride to move out through chloride channels (CFTR) on the apical membrane
307
mutations of what channel cause cystic fibrosis?
CFTR
308
what does cystic fibrosis do to the succus entericus?
decreases the amount
309
what does cholera do to the CFTR channels?
causes them to become over active which causes secretory diarrhoea
310
what hormone from the stomach triggers segmentation in the empty ileum?
(what is this reflex called?)
gastrin
| gastroileal reflex
311
when does peristalsis occur in the small intestine?
in the interdigestive state (between meals)
312
what are the 2 forms of peristalsis in the small intestine?
1. weak infrequent localised contractions
| 2. migrating motor complex
313
what is the migrating motor complex?
a strong peristaltic contraction passing from pyloric sphincter to ileocaecal valve
314
what is the function of the migrating motor complex?
cleans the the small intestine of undigested debris, unabsorbed electrolytes and dead cells
315
what hormone, produced in the small intestine itself, triggers the migrating motor complex?
motilin
316
what hormones supress the migrating motor complex?
gastrin, CCK
317
what is CCK produced in response to?
fats
318
what is the response of the gallbladder to CCK?
contraction
319
what cells secrete digestive enzymes within the pancreas?
acinar cells
320
what cells within the duodenum secrete enterokinase?
mucosal cells (brush border enzyme)
321
why are pancreatic protease enzymes stored as pro-enzymes?
otherwise they would digest themselves and the pancreas wall
322
how is trypsinogen activated into trypsin?
```
enterokinase
trypsin (autocatalysis)
```
323
how is chymotrypsinogen activated into chymotrysin?
trypsin
324
how are procarboxypeptidase A and B activated into carboxypeptidase A and B?
trypsin
325
what cells secrete an alkaline fluid into the duodenum?
duct cells of the pancreas
326
what exchanger sits in the apical membrane of duct cells and allows the transfer of alkaline solution into the lumen of the small intestine?
Cl-/HCO3- exchanger
327
what are the 3 phases of pancreatic secretion?
cephalic
gastric
intestinal
328
what is the cephalic phase of pancreatic secretion mediated by?
vagal stimulation of acinar cells
329
what is the gastric phase of pancreatic secretion mediated by?
gastric distension which evokes a vasovgal reflex. This results in parasympathetic stimulation of acinar and duct cells
330
what hormone is released in response to acid in the duodenal lumen?
secretin from S cells
331
what does secretin cause?
increased secretion of aqueous NaHCO3 solution from pancreatic duct cells
332
what is CCKs role in the pancreas secretion?
increases secretion of digestive enzymes from acinar cells
333
wat is the function of the ileocaecal valve?
stops regurgitation of the colonic content into the ileum
334
what are the 5 main functions of the large intestine?
1. absorption of water and electrolytes
2. secretion of K+, HCO3- and mucus
3. absorption of short chain fatty acids
4. stores colonic contents
5. periodic elimination of faeces
335
why does the large intestine secrete HCO3-?
to neutralise acid produced by bacterial fermentation
336
how do short chain fatty acids form in the colon?
unabsorbed carbohydrates are fermented by colonic flora to short chain fatty acids
337
what are faeces made of?
indigestible residue
bacteria
bilirubin
338
what is haustration of the colon?
non-propulsive segmentation of the colon (slow movement)
339
what direction of movement does haustration cause?
orad movement
(oral direction)
to increase transit time for fluid and electrolyte reabsorption
340
what does the contraction of taenia coli cause?
shortening of the colon
341
what are the 3 patterns of motility in the large intestine?
haustration
peristaltic propulsion
defecation
342
how does defecation occur?
mass movement driving faeces into rectum to trigger defaecation reflex
343
what are the 4 main benefits of colonic symbiotic bacteria?
1. increase intestinal immunity by competition with pathogenic microbes
2. promote motility and help maintain mucosal integrity
3. synthesis vitamin K2 and free fatty acids
4. activate some drugs
344
what is the difference between laxatives and purgatives?
laxatives are used to treat constipation
| purgatives are used to clean bowel by promoting evacuation
345
what are bulk laxatives?
indigestible polysaccharide polymers which improve stool consistency
346
what are osmotic laxatives?
poorly absorbed solutes to improve stool consitency
347
what purgatives are known to cause abdominal cramps?
stimulant purgatives
348
what is the function faecal softners?
lubricate the stool to enable it to pass through intestines easier
349
what is the main adverse effect of faecal softners?
anal sepage
350
what drugs are used to clean bowels before colonoscopy?
stimulant purgatives
351
when are glucocorticoids used in IBD?
for acute flate ups
352
what do aminosalicylates release? (the active molecule)
5ASA
| 5-aminosalicylic acid
353
what UC medications are cleaved by bacteria in order to become activated?
many aminosalicytes
| sulfsalazine, olsalazine, balsalazide
354
how is water transported from the lumen of the intestine to the bloodstream?
passive transport driven by the transport of solutes (particularly Na)
355
what are the 5 ways Na+ gets transported from lumen of the GI tract to the bloodstream?
1. Na+/glucose co-transport
2. Na+/amino acid co-transport
3. Na+/H+ exchange
4. Parallel Na+/H+ and Cl-/HCO3- exchange
5. epithelial Na channels (ENaC)
356
where does Na+/glucose co-transport occur?
throughout small intestine
357
when is Na+/glucose co-transport most important?
postprandially
358
where does Na+/amino acid co-transport occur?
throughout the small intestine
359
when is Na+/amino acid co-transport most important?
postprandially
360
where does Na+/H+ exchange take place?
duodenum and jejunum
361
what is Na+/H+ exchange stimulated by?
luminal (pancreatic) HCO3-
362
where does parallel Na+/H+ and Cl-/HCO3- exchange take place?
ileum and colon
363
when is parallel Na+/H+ and Cl-/HCO3- exchange most important??
interdigestive period
364
where does movement of Na+ through ENaC take place?
colon
365
what is the movement of Na+ through ENaC regulated by?
aldosterone
366
what do intracellular cAMP, cGMP and Ca2+ do to the movement of Na+ and Cl- through Na+/H+ and Cl-/HCO3- exchange?
decrease absorption of NaCl
367
what is the mechanism of how E coli enterotoxin causes diarrhoea?
enterotoxin activates adenylate cyclase which increases intracellular cAMP. this reduces the NaCl absorption causing secretory diarrhoea
368
what are the 3 roles of aldosterone within ENaC channel regulation?
1. opens ENaCs
2. inserts more ENaC into membrane from intracellular vesicle pol
3. increases synthesis of ENaC and Na+/K+ATPase
369
which occurs at the fastest rate: Cl- absorption or Cl- secretion in GI tract?
Cl- absorption occurs at a faster rate than Cl- secretion
370
what is the effect of cAMP, cGMP and Ca2+ on CFTR channels?
up-regulation
371
how does cholera cause diarrhoea?
cholera toxin causes increased activity of adenyl cyclase leading to increased intracellular cAMP, this enhances CFTR leading to hypersecretion of Cl- with Na+ and water following
372
what are the 2 blood supplies to the liver?
```
hepatic portal vein (nutrient rich, oxygen poor)
hepatic artery (oxygen rich)
```
373
where does hepatic portal blood and hepatic artery blood mix?
within liver sinusoids
374
what are the functional units of the liver?
hexagonal lobules
375
what lies in the centre of a liver lobule?
hepatic vein
| central vein
376
a hepatic lobule has a portal triad at each of its six corners. what does this triad contain?
a branch of hte hepatic portal vein
a branch of the hepatic artery
a bile duct
377
nutrients coming into the liver through sinusoids are received by what membrane of hepatocytes?
basolateral membrane
378
what membrane of heaptocytes faces the canaliculi- where bile collects?
apical canaliculi
379
what is the pericellular space between the capillaries (sinusoids) and basolateral membrane of the hepatocytes?
space of Disse
380
what are the 3 types of cells within the sinusoidal space?
endothelial cells
kuppfer cells
stellate (Ito) cells
381
what are kuppfer cells?
macrophages resident to the sinusoidal vascular space
382
where do stellate (ito) cells reside within the sinusoidal space?
within space of Disse
383
what is the main function of stellate (ito) cells?
storage of vitamin A
| play a role in fibrosis and cirrhosis due to storage of collagen
384
why are endothelial cells within the liver sinusoids fenestrated?
to allow for the free movement of solutes
385
what is the pathway of bile from the canaliculi?
```
canaliculi
terminal bile ductules
perilobular ducts
interlobular ducts
septal ducts
lobar ducts
2 hepatic ducts
common hepatic duct
```
386
where is bile stored and concentrated?
gall bladder
387
what causes the gall bladder smooth muscle to contract?
CCK and vagal impulses
388
what 2 secretions does bile consist of?
secretion of hepatocytes
| secretion of bile duct cells (cholangiocytes)
389
what is the secretion from bile duct cells? (cholangiocytes)
an alkaline solution
390
between meals the secretion from bile duct cells has an ionic composition similar to plasma, what causes the solution to become alkaline during meals?
1. secretin released from S cells causes the flow rate to increase
2. increased flow rate increases Cl-/HCO3- exchange, causing HCO3- content of solution to increase
391
what is hepatic bile composed of?
1. primary bile acids
2. water and electolyes
3. lipids and phospholipids
4. cholesterol
5. IgA
6. bilirubin
392
what is the only way cholesterol can be excreted from the body?
through bile
393
what imbalance causes gall stones? (cholelithiasis)
excess cholesterol relative to bile acids may precipitate out and aggregate into gall stones
394
what pharmacological therapy can be used to dissolve non-calcified cholesterol gallstones?
ursodeoxycholic acid
395
how are bile salts secreted from apical membrane of hepatocytes into canalicula?
active transport
396
how are bile salts absorbed in the ileum?
secondary active transport
397
what is the synthesis of primary bile salts from cholesterol initially mediated by?
cholesterol 7alpha-hydroxylase
398
what is rate of synthesis of bile salts dependent upon?
the hepatic portal blood concentration of bile salts
399
what does low concentration of bile salts in the portal blood cause?
stimulates synthesis of bile salts
400
what does high concetration of bile salts in the portal blood cause?
inhibits synthesis of bile salts
401
what is the most common pathology of the biliary tract?
cholelithiasis
| gallstones
402
what is the usual management of cholelithiasis?
surgery
403
what are the main drugs used for the pain of biliary colic?
morphine for analgesia
| atropine or GTN for relief of biliary spasm
404
what is the problem with using morphine fro biliary colic?
morphine can increase presure within biliary tree and constricts sphincter of Oddi
405
what are the 4 mechanisms of drug metabolism within the liver?
1. conversion to a metobilite less pharmacologically active
2. concerstion from inactive prodrug to active compound
3. unchanged activity
4. conversion to a different spectrum of action
406
what are the 2 phases of drug metabolism?
phase 1: oxidation, reduction, hydrolysis
phase 2: conjugation
(although remember some drugs are excreted unchanged)
407
what is the function of phase 1 of drug metabolism?
makes drug more polar thus permitting conjugation
408
what is the function of phase 2 of drug metabolism?
adds an endogenous compound to increase polarity
